This invention relates to compositions and methods capable of detecting cancer cells or malignant tumors in humans. More particularly, this invention relates to compositions radiolabeled with technetium-99m (Tc-99m) which, when administered to a human will accumulate at cells producing human carcinoembryonic antigen (CEA), human alphafetoprotein (AFP), other tumor-associated antigens (TAA) and/or mixtures thereof.
The use of compositions which emit radiation at levels which can be detected after administration to the human body are well known. These compositions are utilized to visualize and/or monitor functioning of various parts of the body or are utilized diagnostically to determine the presence or absence of particular cellular and/or tissue antigens, macromolecules, hormones or the like. In one particular aspect of the prior art, radiolabeled antibodies are utilized to detect tumors having associated therewith CEA. As disclosed in U.S. Pat. Nos. 3,663,684, 3,867,363 and 3,927,193, I.sup.131 or I.sup.125 labeled antibodies are used to detect human malignancy. Antibodies radiolabeled with I.sup.131, I.sup.125 or I.sup.123 have been used to detect murine teratocarcinomas in an in vivo model (Ballou et al, Science, 206, pp. 844-847, 1979).
It is also well known that various molecular proteins, including glycoproteins, lipoproteins and other types of macromolecules can be associated with certain types of cancers, and as such, these molecules can be considered to be tumor-associated antigens (TAA) (Rosenberg, Serologic Analysis of Human Cancer Antigens, Academic Press, New York, 1980.) Examples of TAA include hCG, CEA, AFP and a variety of antigens that have been defined using polyclonal heterologous and monoclonal antibodies that are associated with melanoma, breast cancer, lung cancer, ovary, sarcoma and other types of cancers.
It is also well known that protein molecules can be tagged with Tc-99m to form diagnostic agents, some of which can be used for in vivo scanning agents that can identify human malignancy (Rhodes et al, Basics in Radiopharmacy, C. V. Mosby, St. Louis, 1978). An example of such a composition is Tc-99m labeled human serum albumin (Tc-99m HSA). However, there is no prior art relating to the use of Tc-99m labeled antibody molecules using the preferred procedure discussed in this application.
With regard to hCG, it has been proposed to tag the antibody of the beta-chain of hCG with peroxidase (McManus et al, Cancer Research, 36, pp. 2367-3481, September, 1976) in order to identify the antigen in malignant tumors in vitro. Furthermore, it has been proposed to label the IgG antibody to hCG with radioactive iodine in order to localize the antigen in human choriocarcinomas transplanted in hamster cheek pouches (Quinones et al, Journal of Nuclear Medicine, Vol. 12, pp. 69-75, 1971).
Recently, it has been found that neoplastic tissues produce and/or express on their surface hCG, hCG-like material and a compound similar to and/or identical to the beta-chain of hCG or mixtures thereof, specifically to the degree where it may be considered to be a more general marker than either CEA or AFP (Acevdo et al, "Detection and Prevention of Cancer", Part 2, Vol. I, H. E. Neiburgs (ED), Marcel Dekker, Inc., New York, 1978, pp. 937-979. The positive identification of hCG in a heterogenous group of cancer cells and its non-detection in non-cancer cells in vitro suggests that it may be a useful tumor marker for in vivo imaging.
While peroxidase-labeled or fluorescein-labeled anti-hCG-beta or anti-hCG antibodies are effective for identifying malignant cells, these labeled compositions are undesirable for in vivo use because they do not allow for visualization by any available scintigraphy detection system and are otherwise undesirable for widespread use because they are simply an in vitro immunohistochemical technique requiring light or electron microscopy of biopsy samples for positive identification. In addition, the use of radiolabeled antibodies in scintigraphy wherein the labeled antibody binds directly to the cancer cell having its corresponding antigen, can cause faint and imperfect imaging of the cancer cell or cells since the antibody usually has a limited number of binding sites. Thus, the cell may only be able to accommodate one radiolabeled antibody molecule on a single antigen site. Thus, the density of the radiolabeled molecule on the cell surface may not be sufficient to permit distinction of the cancer cell from surrounding tissues.
Accordingly, it would be highly desirable to provide a class of labeled antibodies which can be utilized in vivo and which overcomes the disadvantages of the prior art compositions.